Critical roles for light and its receptors in generating T cell-mediated immunity during Leishmania Donovani infection

Stanley, AC; de Labastida Rivera, F; Haque, A; Sheel, M; Zhou, Y; Amante, FH; Bunn, PT; Randall, LM; Pfeffer, K; Scheu, S; Hickey, MJ; Saunders, BM; Ware, C; Hill, GR; Tamada, K; Kaye, PM; Engwerda, CR

Critical roles for light and its receptors in generating T cell-mediated immunity during Leishmania Donovani infection

Stanley, AC de Labastida Rivera, F Haque, A Sheel, M Zhou, Y Amante, FH Bunn, PT Randall, LM Pfeffer, K Scheu, S Hickey, MJ Saunders, BM

Ware, C Hill, GR Tamada, K Kaye, PM Engwerda, CR

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Publication Type:: Journal Article
Citation:: PLoS Pathogens, 2011, 7 (10)
Issue Date:: 2011-10-01

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Field	Value	Language
dc.contributor.author	Stanley, AC	en_US
dc.contributor.author	de Labastida Rivera, F	en_US
dc.contributor.author	Haque, A	en_US
dc.contributor.author	Sheel, M	en_US
dc.contributor.author	Zhou, Y	en_US
dc.contributor.author	Amante, FH	en_US
dc.contributor.author	Bunn, PT	en_US
dc.contributor.author	Randall, LM	en_US
dc.contributor.author	Pfeffer, K	en_US
dc.contributor.author	Scheu, S	en_US
dc.contributor.author	Hickey, MJ	en_US
dc.contributor.author	Saunders, BM https://orcid.org/0000-0003-0540-4445	en_US
dc.contributor.author	Ware, C	en_US
dc.contributor.author	Hill, GR	en_US
dc.contributor.author	Tamada, K	en_US
dc.contributor.author	Kaye, PM	en_US
dc.contributor.author	Engwerda, CR	en_US
dc.date.available	2011-08-08	en_US
dc.date.issued	2011-10-01	en_US
dc.identifier.citation	PLoS Pathogens, 2011, 7 (10)	en_US
dc.identifier.issn	1553-7366	en_US
dc.identifier.uri	http://hdl.handle.net/10453/111317
dc.description.abstract	LIGHT (TNFSF14) is a member of the TNF superfamily involved in inflammation and defence against infection. LIGHT signals via two cell-bound receptors; herpes virus entry mediator (HVEM) and lymphotoxin-beta receptor (LTβR). We found that LIGHT is critical for control of hepatic parasite growth in mice with visceral leishmaniasis (VL) caused by infection with the protozoan parasite Leishmania donovani. LIGHT-HVEM signalling is essential for early dendritic cell IL-12/IL-23p40 production, and the generation of IFNγ- and TNF-producing T cells that control hepatic infection. However, we also discovered that LIGHT-LTβR interactions suppress anti-parasitic immunity in the liver in the first 7 days of infection by mechanisms that restrict both CD4 + T cell function and TNF-dependent microbicidal mechanisms. Thus, we have identified distinct roles for LIGHT in infection, and show that manipulation of interactions between LIGHT and its receptors may be used for therapeutic advantage. © 2011 Stanley et al.	en_US
dc.relation.ispartof	PLoS Pathogens	en_US
dc.relation.isbasedon	10.1371/journal.ppat.1002279	en_US
dc.subject.classification	Virology	en_US
dc.subject.mesh	Liver	en_US
dc.subject.mesh	Dendritic Cells	en_US
dc.subject.mesh	T-Lymphocytes	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred C57BL	en_US
dc.subject.mesh	Mice, Knockout	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Leishmania donovani	en_US
dc.subject.mesh	Leishmaniasis, Visceral	en_US
dc.subject.mesh	Interleukin-12	en_US
dc.subject.mesh	Antibodies, Monoclonal	en_US
dc.subject.mesh	Signal Transduction	en_US
dc.subject.mesh	Cell Proliferation	en_US
dc.subject.mesh	Immunity, Cellular	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Interleukin-23	en_US
dc.subject.mesh	Receptors, Tumor Necrosis Factor, Member 14	en_US
dc.subject.mesh	Lymphotoxin beta Receptor	en_US
dc.subject.mesh	Tumor Necrosis Factor Ligand Superfamily Member 14	en_US
dc.subject.mesh	Interferon-gamma	en_US
dc.title	Critical roles for light and its receptors in generating T cell-mediated immunity during Leishmania Donovani infection	en_US
dc.type	Journal Article
utslib.citation.volume	10	en_US
utslib.citation.volume	7	en_US
utslib.for	0605 Microbiology	en_US
utslib.for	1107 Immunology	en_US
utslib.for	1108 Medical Microbiology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access
pubs.issue	10	en_US
pubs.publication-status	Published	en_US
pubs.volume	7	en_US

Abstract:

LIGHT (TNFSF14) is a member of the TNF superfamily involved in inflammation and defence against infection. LIGHT signals via two cell-bound receptors; herpes virus entry mediator (HVEM) and lymphotoxin-beta receptor (LTβR). We found that LIGHT is critical for control of hepatic parasite growth in mice with visceral leishmaniasis (VL) caused by infection with the protozoan parasite Leishmania donovani. LIGHT-HVEM signalling is essential for early dendritic cell IL-12/IL-23p40 production, and the generation of IFNγ- and TNF-producing T cells that control hepatic infection. However, we also discovered that LIGHT-LTβR interactions suppress anti-parasitic immunity in the liver in the first 7 days of infection by mechanisms that restrict both CD4 + T cell function and TNF-dependent microbicidal mechanisms. Thus, we have identified distinct roles for LIGHT in infection, and show that manipulation of interactions between LIGHT and its receptors may be used for therapeutic advantage. © 2011 Stanley et al.

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http://hdl.handle.net/10453/111317